We have found that small increases in extracellular K ion concentrations significantly increase the rate of protein synthesis in tissue slices from neocortex and hippocampus of the rodent. The fact that these increases in (K ion) approximate those which occur in situ during normal electrophysiological activity suggest that this effect may be a mechanism by which electrical activity and protein synthesis are coupled in brain. We propose to carry out experiments to define the role that this interaction may be playing in the function of brain cells in situ. Four hypotheses relative to this will be tested: 1) that protein synthesis is activated in nerve cells rather than in glial cells; methods used will be standard cell separation techniques and, if necessary, radioautography. 2) in order to see whether the effect of (K ion) on synthesis is leading to maintenance (or trophic) effects on cells or is likely to be leading to specific functional changes, the proteins whose synthesis is activated by (K ion) will be characterized by determining the subcellular fractions in which they exist and within these fractions it will be determined whether essentially all or only a small number of proteins are affected; standard subcellular fractionation techniques and gel electrophoresis techniques will be used. 3) that protein synthesis is activated as a result of K-induced membrane depolarization; intracellular recordings will be made to find concentrations of drugs which will depolarize the membrane to the same extent as increased (K ion). Effects of these drugs on protein synthesis will then be tested. 4) that increased extracellular (K ion) will activate protein synthesis in situ; superfusion of cortex with elevated (K ion) buffers will be used to increase cortical extracellular (K ion). These experiments should: 1) serve to show whether or not the effect of extracellular (K ion) on synthesis is likely to be expressed in vivo and 2) define, in a general way, the role that this effect is likely to be playing in cerebral cell functions. They will provide the basis for further work toward specifying this role.